In reconstructive surgery, a long random skin flap is ofter required for closure of wounds in the head, neck, chest or arm. Clinically and experimentally, surgical "delay procedure" (delayed flap) is the only proven technique in obtaining a greater length of skin viability than can be obtained safely by a single stage operation (acute flap). So far, there is no satisfactory explanation for the "delay pnenomenon." The general consensus is that the length of skin viability in a random flap is related to the extent of nutrient (capillary) blood flow. The aims of this proposed research are to obtain information on the pathophysiology of cutaneous circulation and the control mechanism thereof in acute and delayed random skin flaps in pigs. Specifically, we plan to examine and/or compare the following parameters in the normal intact skin and in the skin of acute and delayed random skin flaps in pigs: (i) the nutrient and arteriovenous (AV) shunt flow at various time points after surgery; (ii) the relationship between nutrient blood flow and plasma and skin tissue prostaglandin levels in skin flap viability; (iii) the roles of sympathetic nervous system and alpha-adrenergic receptor binding activity in regulation of cutaneous blood flow; and (iv) the effectiveness of vasodilating and antithrombotic prostaglandins (PGE2, PGI2) and/or their synthesis inhibitor (indomethacin) in augmentation of cutaneous blood flow and skin viability in skin flaps. These approaches may help us to understand the delay phenomenon in skin flap surgery and may also lead to the identification of pharmacological agents and their site of action in increasing skin blood flow and skin viability in acute flaps. The ultimate goal is to use pharmacological manipulations instead of delay procedure to increase random skin flap viability in reconstructive surgery. The latter is timeconsuming and costly because it requires a long period of hospitalization and extra medical care. Major techniques required in this proposal are: (i) measurement of nutrient and AV shunt flow by radioactive microsphere technique; (ii) RIA's for PGF2alpha, PGE2, 6-Keto PGF1alpha, TxB2, and catecholamines; and (iii) radioligand binding assay for alpha-adrenergic receptors.